Process for the production of unsaturated delta-decalactone



United States Patent 3,531,501 PROCESS FOR THE PRODUCTION OF UNSATURATED fi-DECALACTONE Lambertus Gerke Heeringa, Middletown, Robert J. Fehn, Holmdel, James D. Grossman, Elizabeth, and Braja D. Mookherjee, Keyport, N.J., assignors to International Flavors & Fragrances Inc., New York, N.Y., a corporation of New York No Drawing. Filed Oct. 16, 1967, Ser. No. 675,292 Int. Cl. C07d 7/06 US. Cl. 260-3435 6 Claims ABSTRACT OF THE DISCLOSURE Process for the preparation of unsaturated B-decalactone which comprises reacting an alkynylcyclopentanone with an aliphatic percarboxylic acid at about 10 to about 50 C. and, if desired, partially hydrogenating the fi-alkynyllactone so obtained to produce a fi-alkenyllactone.

BACKGROUND OF THE INVENTION In view of the limited availability of natural jasmin, and its commercial importance in producing high grade fragrances, synthetic substitutes have become desirable. Since certain lactones constitute part of the fragrance impression of jasmin, and 2-(cis-penten-2'-yl-l) pentanolide, the fi-lactone of 5-hydroxy-7-decenoic acid, is known to constitute an important constituent of the essence of Italian jasmin, a commercially feasible synthesis for this lactone has been sought.

A number of routes for the production of such lactones from various starting materials are available, although they are rather complicated. One of the known methods of synthesis for the (i-lactone of 5-hydroxy-7-decenoic acid begins with the reaction of cyclopentanone with pyrrolidine to form pyrrolidylcyclopentene, and subsequent treatment of the unsaturated alicyclic ring with bromopentyne to provide pentynylcyclopentanone. The prior art suggests that a Baeyer-Villiger reaction could be used to produce the lactone from the pentynylcyclopentanone, but the prior art further demonstrated that treating alkynylcyclopentanone with peracids provided a mixture of materials without the formation of any detectible amounts of the desired lactone. In order to produce the desired intermediate, a multistep method was devised by E. Demole et al. and reported in Helvetica Chimica Acta 45, 1256 (1962).

In showing a synthesis for the lactone, Demole et al. disclosed that attempts to oxidize the material to the lactone directly utilizing either perbenzoic acid, metachloroperbenzoic acid, or trifluoroperacetic acid, all of which were thought to be reagents specific to oxidize the ring and thereby produce the lactone, were unsuccessful. Accordingly, the synthesis finally arrived at utilized a complex process involving reduction of the acetylenic bond in the pentynylcyclopentanone, formation of the cyclic alcohol, bromination and lactone formation, followed by a reduction to obtain the unsaturated lactone ring.

THE INVENTION The invention accordingly comprises the novel processes and steps of processes, specific embodiments of which are described hereinafter by way of example and in accordance with which it is now preferred to practice the invention.

Briefly, the process of this invention comprises treating alkynylcyclopentanone with certain unsubstituted aliphatic percarboxylic acids at temperatures in the range of from about to about 50 C. to form the alkynyl 6-lactone.

Patented Sept. 29, 1970 The alkynyllactone so formed can be further selectively hydrogenated to provide the alkenyl derivatives. Such 6-alkenyllactones are useful in the preparation of perfumes and fragrance compositions, as further described herein.

The alkynylcyclopentanones treated according to the present invention include 2-(pentyn-2-yl) cyclopentanone. It is preferred that the starting material be relatively pure to avoid the formation of unwanted byproducts and to facilitate purification of the desired lactone. Such alkynylcyclopentanones can readily be prepared by treating cyclopentanone with a secondary amine such as pyrrolidine or piperidine under acidic conditions to form the corresponding enamine such as 1-pyrrolidylcyclopentene-1 and subsequently alkylating the enamine so obtained with l-bromopentyne-2.

The choice of the percarboxylic acid is most important in obtaining any significant yield of the desired product from the reaction, and accordingly aliphatic percarboxylic acids are used. The lower aliphatic percarboxylic acids having up to about four carbon atoms are most desirable, and performic, peracetic, and perpropionic acids are preferred. The best results are generally obtained with peracetic acid. The term aliphatic as used herein to describe the percarboxylic acids utilized in the practice of this process will be taken to exclude substituted percarboxylic acids such as monoor polyfluoro-, hydroxy-, methoxy-, and amino-substituted acids and the like.

The yield of alkynyl lactone can be improved or the rate of reaction can be increased by incorporating catalytic amounts of certain strong protonic acids into the reaction system. These protonic acids may be added directly into the system or may first be mixed with the peracid material. When such protonic acids are used, only small amounts are required, that is, up to about 0.5% of the percarboxylic acid. It is especially preferred to utilize as strong protonic materials sulfuric acid and organic sulfonic acids such as methane sulfonic, p-toluene sulfonic, and the like. Unless otherwise indicated, all ratios, proportions, parts, and percentages herein are by weight.

The yield of the reaction is also affected by the amount of aliphatic percarboxylic acid present in the reaction mixture. If too small a quantity of the percarboxylic acid is present the yields are lower and the alkynylcyclopentanone starting material must be recovered. On the other hand, the use of too much percarboxylic acid causes side reactions which lower the yield. It is accordingly desirable to utilize an approximately equimolar quantity of the percarboxylic acid, and slight excesses of the per carboxylic acid up to about 40 molar percent are preferred.

It has been found that at temperatures below 10 C. the quantity of the desired material formed is generally significant. As the temperature is increased to 10 C. and above, however, it has been discovered that the yields are substantially increased, and a temperature of 25 C. or more is preferred. At temperatures in excess of about 50 C., the acetylenic bond is attacked and the yields once again become less satisfactory. Accordingly, it is preferred in the practice of this invention to conduct the reaction at temperatures of from 10 C. to about 50 C., and it is especially preferred to conduct the reaction at temperatures of from about 25 C. to about 45 C.

It is preferred to carry out the lactone formation under atmospheric pressure. The reaction can be carried out in the presence of an inert atmosphere such as nitrogen although this is not generally necessary or advantageous. If desired, an inert vehicle, for example an aromatic material such as toluene and the like, can also be incorporated in the reaction mixture.

The time of the reaction varies according to the temperature at which the reaction is carried out, the purity of the ingredients, the completeness of reaction desired, the presence of inert vehicle, if any, and the agitation utilized. It is desirable to conduct the reaction for times ranging from about two to about ten hours, shorter times producing lower yields and longer times giving no further advantage in the production of the desired lactone. The reaction is conveniently carried out by adding the percarboxylic acid slowly over a period of time and then holding the reaction mixture under agitation until the desired completeness of reaction is obtained. The progress of the reaction can be readily followed by analyzing small quantities of the reaction mixture, for example, by gas-liquid chromatography (GLC).

The alkynylacetone is extracted with water-benzene mixture to remove water-soluble impurities, and the organic layer so obtained is washed with an alkaline material, preferably the salt of a strong base and a weak acid, for excess acid removal. The material can then be washed with salt solution for further purification. It can thereafter be dried, filtered, and stripped of the benzene or other solvent. The alkynyllactone product can further be treated, as by hydrogenation, or it can be purified by conventional techniques such as selective extraction, fractional distillation, and the like.

The alkynyllacetone produced can be selectively hydrogenated in high yield to produce the corresponding alkenyllactone. In order to obtain the preferred alkenyl material having a preponderance of cis isomers in good yield, it is desirable to add not more than one mol of hydrogen per mol of alkynyllactone. The hydrogenation reaction is carried out in the presence of Lindlar catalysts such as palladium on calcium carbonate and the like, which are selective in maximizing the yield of alkenyl material and minimizing the yield of other hydrogenation products such as alkane-lactone and transalkenyllactones. Suitable pressures are in the range of from about 2 to about 50 p.s.i.g. The temperatures suitable in carrying out the reaction are in the range of from about 25 C. to about 60 C.

It is generally preferred to perform the hydrogenation at a relatively low temperature while hydrogen is slowly added, and then to maintain the temperature of the reaction mass after the mol of hydrogen has been introduced so as to insure a high completeness of reaction. It is frequently desirable to carry out the hydrogenation in the presence of an inert vehicle, such as alcohol and the like.

Similarly, the cis-alkenyllactone obtained by hydrogenation is filtered to remove the hydrogenation catalyst and can be washed or further treated as desired to provide a substantially pure material.

The decenoic acid fi-lactone produced according to the present invention has a pronounced jasmin fragrance and is suitable for use as a fragrance material itself, as a component of fragrance compositions, or as a component of perfume compositions. Thus, the materials of this invention are useful as olfactory agents and fragrances.

The term perfume composition is used herein to mean a mixture of compounds, including, for example, natural oils, synthetic oils, alcohols, aldehydes, ketones, esters, other lactones, and frequently hydrocarbons which are admixed so that the combined odors of the individual components produce a pleasant and desired fragrance. Such perfume compositions usually contain: (a) the main note (the bouquet or foundation-stone) of the composition; (b) modifiers which round off and accompany the main note; (c) fixatives including odorous substances which lend a particular note to the perfume throughout all stages of evaporation and substances which retard evaporation; and (d) top-notes which are usually lowboiling fresh-smelling materials. Such perfume compositions or the materials of this invention can be used in conjunction with carriers, vehicles, solvents, dispersants, emulsifiers, surface-active agents, aerosol propellants, and the like.

In perfume compositions the individual components contribute their particular olfactory characteristics, but the overall effect of the perfume composition can be more than the sum of the effect of each ingredient. Thus, the individual compounds of this invention, or mixtures thereof, may be used to alter the aroma characteristics of a perfume composition, for example, by high-lighting or moderating the olfactory contribution of another ingredient in the composition.

The amount of the compounds obtained according to this invention which will be effective in perfume compositions depends on many factors, including the other ingredients, their amounts, and the effects which are desired. It has been found that perfume compositions containing as little as 0.5% by weight of the compounds produced according to the process of this invention, or even less, can be used to impart a jasmin odor to soaps, cosmetics and similar products. The amount employed will depend on considerations of cost, nature of the end product, the effect desired on the finished product and the particular fragrance sought.

The materials disclosed herein can be used alone, in a fragrance-modifying composition, or in a perfume composition as olfactory components in detergents and soaps; space deodorants; perfumes; colognes; bath preparations such as bath oil and bath salts; hair preparations such as lacquers, brilliantines, pomades, and shampoos; cosmetic preparations such as cremes, deodorants, hand lotions, and sun screens; powders such as talcs, dusting powders, and face powders; and the like.

The following examples serve to illustrate embodiments of the invention as it is now preferred to practice it. It will be understood that these examples are illustrative and are to be considered restricted thereto only as indicated.

EXAMPLE I Preparation of alkynyllactone A 50 ml. Erlenmeyer flask is fitted with a stirrer, a thermometer, and cooling means, and 15 g. (0.1 mol) of pentynylcyclopentanone as prepared above is introduced into the flask. The flask is cooled to maintain a temperature of 2025 C. while 21 g. (0.11 mol) of 40% peracetic acid containing about 1% sulfuric acid is added over a 45-minute period. The mass is then maintained under agitation for three hours, at which point the GLC monitoring indicates formation of the desired product with a small amount of the original starting material still present. Accordingly, 7 g. (0.037 mol) of 40% peracetic acid is added, and the mixture is stirred for an additional one hour.

At the end of the additional one-hour stirring period, the reaction mixture is transferred to a separatory funnel, and an equal volume of water and 50 ml. of benzene are added. After mixing, the upper organic layer is separated from the aqueous layer and washed three times with 50 ml. of 5% aqueous sodium bicarbonate. The organic layer is further washed twice with 50 ml. of aqueous saturated sodium chloride, dried over anhydrous magnesium sulfate and filtered. The benzene is then removed on a rotary evaporator. Instrumental analysis shows the major product formed is the a-lactone of 5- hydroxy-7-decynoic acid having the structure EXAMPLE II Preparation of alkynyllactone Two equal portions of 28.5 g. (0.16 mol) of pentyny.- cyclopentanone are treated with 35 g. (0.18 mol) of 40% peracetic acid containing about 1% sulfuric acid so that the peracetic acid is in approximately 16% excess over the theoretical amount. In each instance the peracetic acid is added to the cyclopentanone at 20-25 C.

5 over a one-hour interval. The reaction mixtures are stirred for approximately five hours, while the course of the reaction is monitored by GLC analysis of the reaction mixture.

After the five-hour period 50 ml. of an aqueous 50% saturated salt solution is added to each reaction mixture together with 25 ml. of benzene. The organic layers in each of the two vessels are separated and washed three times with 100 ml. of aqueous 50% saturated sodium chloride solution and then once with saturated sodium chloride solution. The washed mixtures are dried over anhydrous magnesium sulfate and filtered. The fractions are then distilled on a micro still to obtain pure product.

This material is substantially the pure a-lactone of 5-hydroxy-7-decynoic acid.

Similar results are obtained by substitution of perpropionic acid for peracetic acid.

Selective hydrogenation The lactone prepared above in the amount of 27.5 g. is then placed in a Parr reaction vessel with 20 g. of isopropanol and 0.3 g. of a palladium on calcium carbonate catalyst. The mixture is hydrogenated with 0.15 mol of hydrogen at 27-55 C. with a pressure falling from 49 to 36 p.s.i.g. over the reaction period.

After hydrogenation the material from the Parr apparatus is filtered to remove solids, and the isopropanol is recovered on a rotary separator. The mixture is then distilled on a micro still at a temperature of 108117 C. at 0.5 mm. Hg. GLC analysis shows the reaction products to be approximately 60% f the desired cis isomer and 30% of the trans isomer of the fi-lactone of hydroxy-7-decenoic acid. The liquid pure cis isomer has an 11 of 1.4860.

In other hydrogenations conducted according to the foregoing procedure, the product assayed 90% cis isomer with smaller amounts of the trans isomer and saturated material.

EXAMPLE III The procedure of Example II is repeated with 40% peracetic acid containing no sulfuric acid. Substantially the same yields are obtained, and the reaction velocity appears to be somewhat lower.

EXAMPLE IV To a 500 ml. reaction flask containing 143 g. of pentynylcyclopentanone is added 200 g. of 40% peracetic acid containing about 1% sulfuric acid during a threehour and fifty-three minute period at 24-30 C. The reaction mixture is constantly stirred and mild cooling is applied to maintain the temperature at approximately 30 C. Thereafter the reaction mass is stirred for three hours at 27-44 C while the course of the reaction is monitored by GLC.

The reaction mixture is then treated with 250 ml. of ether and 250 ml. of 50% saturated sodium chloride solution, washed, and settled to separate the organic layer. The organic layer is washed five more times with 250 ml. of 50% saturated sodium chloride solution and then twice with 250 ml. of saturated sodium chloride solution. The washed material is dried over magnesium sulfate and filtered, and the solvent is stripped off with a rotary evaporator.

The mixture is then distilled at 159-186 C. at 0.8-

2.1 mm. Hg. The reaction yields 87 g. (0.525 mol) of the a-lactone of 5 hydroxy 7 decynoic acid of 97% purity.

It will further be understood from the present disclosure that the percarboxylic acid can be formed in situ from an aliphatic earboxylic acid and a, peroxygen compound such as hydrogen peroxide and the like. This technique can be used to obtain any of the percarboxylic acids according to the present invention and it is especially useful when the aliphatic percarboxylic acid is not readily available or when the percarboxylic acid is rela- EXAMPLE V Lactone preparation with carboxylic acid and peroxide mixture A 200 ml. reaction flask is equipped with a stirrer, dropping funnel, and thermometer, and 15 g. (0.1 mol) of pentynylcyclopentanone and 50 g. of formic acid are introduced into the flask. The flask and its contents are then cooled to 20 C. and 7.8 g. of 50% hydrogen peroxide is added to the cooled contents during a forty-five minute period. The temperature of the reaction mixture is then allowed to rise to 35 C., and the contents are stirred for an additional 2.5 hours.

Instrumental analysis shows the formation of substantial quantities of the a-lactone of 5 hydroxy 7 decynoic acid.

EXAMPLE VI The following perfume composition illustrates the use of compositions made by the process of this invention.

Ingredient: Amount (percent by wt.) Phytol 25 Phytyl acetate 10 Hexyl cinnamic aldehyde 6 Benzyl acetate 30 Benzyl alcohol 5 Benzyl benzoate 10 Indole 0.5 Hexenyl pentanone 1.5 Linalool 10 fi-Lactone of 5-hydroxy-7-decenoic acid produced according to the process of Example II 2 The foregoing perfume formulation is an important part of the fragrance of absolute essence of jasmin flower. This perfume composition is incorporated into a soap formulation at the 0.1% level to provide an excellent jasmin scent in the soap.

What is claimed is:

1. A process for the production of an unsaturated lactone which comprises reacting 2(pentyne 2' yl)cycl0- pentanone with a lower alkyl percarboxylic acid at a temperature of from about 10 C. to about 50 C. to obtain the fi-lactone of 5-hydroxy-7-decynoic acid.

2. The process of claim 1 wherein the percarboxylic acid is performic acid, peracetic acid, or perpropionic acid.

3. The process of claim 1 wherein the percarboxylic acid is peracetic acid.

4. The process of claim 1 wherein the reaction is carried out at from about 25 to about 45 C.

5. The process of claim :1 wherein an excess up to 40% of percarboxylic acid is present.

6. A process according to claim 1 wherein the 6-lactone of 5 hydroxy 7 decynoic acid obtained is catalytically hydrogenated with about one mol of hydrogen to produce the fi-lactone of 5-hydroxy-7-decenoic acid.

References Cited UNITED STATES PATENTS 2,362,408 11/1944 Ruzicka 260343.5

ALEX MAZEL, Primary Examiner J. A. NARCAVAGE, Assistant Examiner US. Cl. X.R. 

